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Purpose To determine the accuracy of 18F-fluorodeoxyglucose with positron emission tomography and computed tomography (FDG-PET/CT) scans in assessing the response to neoadjuvant chemotherapy (NAC) in patients with bladder cancer scheduled to undergo radical cystectomy (RC). Patients and Methods All patients treated at our center for muscle-invasive bladder cancer (MIBC) were counseled and offered NAC before RC. FDG-PET/CT scans were performed before the initiation of chemotherapy and after completion of the regimen. Patients with disease with complete response to NAC were those who had (pT0) or residual carcinoma-in-situ (pTis) on final pathology. Those who were downstaged from MIBC to non-MIBC were considered to have a chemosensitive tumor. We used percentage reduction in standardized maximum uptake value (SUVmax) from PET/CT scans as our measure to correlate with the final pathology after cystectomy. Results Thirty-seven patients with MIBC who underwent NAC followed by RC were included in the final analysis. FDG-PET/CT had 75% sensitivity (89.66% specificity) in identifying those with complete pathologic response with a 100% change in SUVmax, and 83% sensitivity (94% specificity) for the detection of chemosensitive tumors. Conclusion FDG-PET/CT can help determine the response of primary tumor to NAC in patients with MIBC and thus can more accurately predict the prognosis of the patients, or potentially the appropriate time for cystectomy.

Magnetic resonance imaging is being widely adopted in the clinical management of prostate cancer. The correlation of the Prostate Imaging Reporting and Data System (PIRADS) to the presence of cancer has been established but studies have primarily evaluated this in a single clinical setting. This study aims to characterize the correlation of PIRADS score to the diagnosis of cancer on fusion biopsy among men who are undergoing primary biopsy, those who have had a previous negative biopsy or men on active surveillance. A consecutive sample of men undergoing US-MR biopsy at a single academic institution from 2014 to 2017 were included in this retrospective study. Men were stratified into groups according to their clinical history: biopsy-naive, previous negative transrectal ultrasound (TRUS) biopsy or on active surveillance. The correlation of PIRADS score to the diagnosis of any and clinically significant cancer (Gleason score ≥ 3 + 4) was determined. A total of 255 patients with 365 discrete lesions were analyzed. PIRADS score 1–2, 3, 4 and 5 yielded any prostate cancer in 7.7, 29.7, 42.3 and 82.4% of the cases, respectively, across all indications while clinically significant cancer was found in 0, 8.9, 21.4 and 62.7%, respectively. The area under the receiver operative curves for the diagnosis of any and significant cancer was 0.69 (95%CI: 0.64–0.74) and 0.74 (95%CI: 0.69–0.79) respectively. Men who have had a previous negative biopsy had lower detection rates for any prostate cancer for PIRADS 3 and 4 lesions compared to those that were biopsy-naive or on active surveillance. Cancer detection rates are significantly associated with PIRADS score. Biopsy yields differ across biopsy indications which should be considered when selecting a PIRADS score threshold for biopsy. Biopsy of PIRADS 3 lesions could potentially be avoided in men who have previously undergone a negative TRUS biopsy.

BACKGROUND With almost 30,000 deaths per year, prostate cancer is the second-leading cause of cancer-related death in men. Androgen Deprivation Therapy (ADT) has been the corner stone of prostate cancer treatment for decades. However, despite an initial response of prostate cancer to ADT, this eventually fails and the tumors recur, resulting in Castration Resistant Prostate Cancer (CRPC). Triptolide, a diterpene triepoxide, has been tested for its anti-tumor properties in a number of cancers for over a decade. Owing to its poor solubility in aqueous medium, its clinical application had been limited. To circumvent this problem, we have synthesized a water-soluble pro-drug of triptolide, Minnelide, that is currently being evaluated in a Phase 1 clinical trial against gastrointestinal tumors. In the current study, we assessed the therapeutic potential of Minnelide and its active compound triptolide against androgen dependent prostate cancer both in vitro as well as in vivo. METHODS Cell viability was measured by a MTT based assay after treating prostate cancer cells with multiple doses of triptolide. Apoptotic cell death was measured using a caspase 3/7 activity. Androgen Receptor (AR) promoter-binding activity was evaluated by using luciferase reporter assay. For evaluating the effect in vivo, 22Rv1 cells were implanted subcutaneously in animals, following which, treatment was started with 0.21 mg/kg Minnelide. RESULTS Our study showed that treatment with triptolide induced apoptotic cell death in CRPC cells. Triptolide treatment inhibited AR transcriptional activity and decreased the expression of AR and its splice variants both at the mRNA and the protein level. Our studies show that triptolide inhibits nuclear translocation of Sp1, resulting in its decreased transcriptional activity leading to downregulation of AR and its splice variants in prostate cancer cells. In vivo, Minnelide (0.21 mg/kg) regressed subcutaneous tumors derived from CRPC 22RV1 at our study endpoint. Our animal studies further confirmed that Minnelide was more efficacious than the standard of care therapies, Docetaxel and Enzalutamide. CONCLUSION Our study indicates that Minnelide is very effective as a therapeutic option against CRPC at a dose that is currently tolerated by patients in the ongoing clinical trials. Prostate © 2017 Wiley Periodicals, Inc.

Objective A number of studies have described the overall institutional learning curve for magnetic resonance imaging-guided biopsy but none have evaluated differences and interactions between clinicians. Therefore, we aim to measure and compare the cancer detection rates between individual radiologists and urologists at a single academic institution. Methods A consecutive sample of patients undergoing magnetic resonance imaging-guided biopsy at a single institution were included for analysis. The detection of any and clinically significant (Gleason score ≥3+4) prostate cancer was compared between radiologists and urologists after adjusting for relevant demographic and clinical characteristics. Analysis was conducted on a perlesion basis and only the results of the targeted cores were considered in the primary analysis. Results Two hundred eighty-one patients with 418 lesions were included in the study. Prostate cancer of any grade was detected in 43.7% (183/418) of targeted lesions. There was no difference in the distribution of Prostate Imaging Reporting and Data System (PIRADS) scores attributed by each radiologist (p = 0.43). The individual radiologist cancer detection rate for both overall and clinically significant cancer was similar across each PIRADS score except for the detection of any cancer in PIRADS 3 lesions (p = 0.03). There was no difference in the detection rates of any grade or clinically significant cancer between urologists. Conclusion This single institutional analysis found that the performance of radiologists and urologists was largely comparable. Theonly variation observed was among radiologists for PIRADS 3 lesions.

Purpose Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism, is a common cause of morbidity and mortality after radical cystectomy. The purpose of our study was to evaluate the utility of extended outpatient chemoprophylaxis against VTE after radical cystectomy—with a focus on any reduction in the incidence of VTE, including DVT and pulmonary embolism. Materials and methods Beginning in April 2013, we prospectively instituted a policy of extending inpatient VTE prophylaxis with subcutaneous heparin/enoxaparin for 30 days postoperatively. For this study, we reviewed the electronic medical records of all patients who underwent radical cystectomy at our institution from January 2012 through December 2015. The experimental group (n = 79) received extended outpatient chemoprophylaxis against VTE; the control group (n = 51) received no chemoprophylaxis after discharge. The primary outcome was the 90-day incidence of VTE. The secondary outcomes included the overall complication rate, the hemorrhagic complication rate, as well as the rate of readmission within 30 days of hospital discharge. Results The experimental group experienced a significantly lower rate of DVT (5.06%), assessed as of 90 days postoperatively, than the control group (17.6%): a relative risk reduction of 71.3% (P = 0.021). We found no significant differences in secondary outcomes between the 2 groups, including the overall complication rate (54.4% vs. 68.6%), the hemorrhagic complication rate (3.7% vs. 2.0%), and the readmission rate (21.5% vs. 29.4%). Conclusion Extended outpatient chemoprophylaxis significantly reduced the incidence of VTE.

476 Background: Accurate grading and staging from transurethral resection of bladder tumors (TURBT) is vital for appropriate clinical management. Non-muscle-invasive bladder cancer (NMIBC) can recur progress with higher grade and or stage progression to MIBC, requiring radical intervention with poorer prognosis. Further, grade and stage may change in 20-50% of TURBTs following re-review by expert GU pathologists Objective measures of stage and grade might offer additional and/or improved risk stratification; therefore we evaluated a molecular RNA signature as a prognostic marker for NMIBC. Methods: Patients were diagnosed with NMIBC at the University of Minnesota (UM)or Spectrum Health System(SHS) from 2005-2012. A Cell Cycle Progression (CCP) score was determined from the average expression of 36 CCP genes for patients with available FFPE diagnostic TURBT. The combined cohort consisted of 293 patients (UM n = 152, SHS n = 141). Study outcome was time from NMIBC diagnosis to progression to MIBC. Median follow-up for patients who did not experience an event was 4.4 years for UM and 6.9 for SHS. Association with outcomes was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. All analyses were stratified by cohort. Results: CCP score was associated with progression to MIBC in univariable analysis [hazard ratio 1.42 (95% CI 1.19, 1.68), p = 4.3x10-5]. Tumor grade and stage were also highly prognostic. CCP score was strongly associated with stage (T1 vs Ta, p < 10-6) and grade (high vs low, p < 10-14) in both cohorts. As a result, CCP score did not provide independent prognostic information in multivariable analysis after adjusting for stage and grade (p = 0.32). There was a significant interaction between stage and CCP score (p = 0.0017), justifying an exploratory analysis of CCP score in Ta disease. In this subset, CCP score trended toward (p = 0.056) after adjusting for grade. Conclusions: In NMIBC, CCP score was highly correlated with tumor stage and grade and could serve as a quantitative measure of clinical parameters. The score may also provide prognostic information regarding risk of progression to MIBC, particularly in patients with Ta disease, but requires additional validation.

Introduction Patients who undergo surgical treatment for malignancy often receive perioperative blood transfusion (PBT). We examined the association between PBT and mortality in patients who received surgical treatment of prostate, bladder, and kidney cancer. Materials and Methods Using the Surveillance, Epidemiology, and End Results-Medicare data set from 1992-2009, we identified 28,854 men with prostate cancer, 5462 patients with bladder cancer, and 14,379 patients with renal cell carcinoma who underwent radical prostatectomy (RP), radical cystectomy (RC), or radical (RN) or partial nephrectomy (PN) as primary therapy. Univariate and multivariate models were used to evaluate the association of PBT with cancer-specific mortality (CSM) and all-cause mortality (ACM). Results The rate of PBT in bladder and kidney cancer have been increasing over time, and PBT in prostate cancer steadily increased and peaked in 2002 and declined afterward. The median follow-up for the RP, RC, and RN/PN cohorts were 70 months, 21 months, and 39 months, respectively. In the RP cohort, PBT was associated with greater CSM (hazard ratio [HR], 1.609; 95% confidence interval [CI], 1.235-2.097; P = .0004) and ACM (HR, 1.121; 95% CI, 1.006-1.251; P = .0394). In the RC cohort, PBT was not associated with greater CSM (HR, 1.047; 95% CI, 0.917-1.195; P = .4962) or ACM (HR, 1.095; 95% CI, 0.998-1.200; P = .0547). In the nephrectomy cohort, PBT was associated with greater CSM (HR, 1.365; 95% CI, 1.167-1.597; P = .0001) and ACM (HR, 1.402; 1.273-1.544; P Conclusion PBT was associated with increased CSM and ACM for prostate and kidney cancer in a multivariate model. Although these data do not identify a causative relationship between PBT and mortality, efforts made to limit PBT in patients who undergo urologic cancer surgery can yield long-term survival benefits.

Men who are elderly constitute a unique patient group who are often denied effective treatments for fear of toxicity or diminished efficacy or are unduly subjected to intense therapies despite multiple comorbidities and indolent disease. This Review highlights the importance of individualizing therapy based on the comorbidities, functional status, nutritional status and aggressiveness of disease rather than age alone. The incidence of prostate cancer increases with age. Current evidence suggests that prostate cancer is under treated in patients aged ≥70 years, despite evidence of efficacy and acceptable toxicity. Radical cystectomy and definitive radiotherapy are often denied owing to fears of post-operative complications and radiotherapy-associated gastrointestinal and genitourinary toxicity. However, modern radical prostatectomy techniques provide excellent clinical outcomes with low perioperative morbidity. Moreover, volume-restricted intensity-modulated radiation therapy is a significant improvement over previous 2D conformal radiotherapy with similar efficacy and lower toxicity. Androgen-deprivation therapy is also under-prescribed among the elderly, owing to concerns of increases in cardiac deaths and osteoporosis acceleration. However, prospective trials have not identified any increase in cardiovascular mortality among elderly men receiving androgen-deprivation therapy compared to age-matched controls. Most patients on androgen deprivation eventually progress to a castration-resistant state. At this stage, the disease still responds to newer agents that target the androgen pathway and to chemotherapy. Among the elderly, chemotherapy is under-prescribed even though it has been demonstrated to be palliative and improve survival. We describe the trends in prostate cancer management in the elderly and the importance of assessing comorbidity status, tumour characteristics, and health status, including a complete geriatric evaluation, before making treatment recommendations.

The precise utility of positron emission tomography (PET) scanning for urologic cancers is not well defined. We examined the trends of usage in a population-based data set. PET scans were performed in 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with renal cell carcinoma. This selective usage might be driven by reimbursement constraints or identification of appropriate medical indications.Positron emission tomography (PET) scanning is increasingly being used for imaging a variety of cancers, including urologic cancers. The precise utility of PET scanning for bladder cancer, prostate cancer, and renal cell carcinoma (RCC) is not yet well known. We examined the trends in PET scan usage for 3 cancers using a large population-based data set.We analyzed all individuals identified with a diagnosis of nonmetastatic bladder cancer, prostate cancer, and RCC from the Surveillance, Epidemiology, and End Results-Medicare data set for 2004 to 2009 with follow-up data available to 2010. Logistic regression analysis and χ(2) and trend tests were performed to determine the predictors of performing PET scanning. Separate models were run for each of the cancer diagnoses. All analyses were performed using SAS, version 9.3, and P.05 was considered significant.We identified 20,865, 70,414, and 7007 patients with a diagnosis of bladder cancer, prostate cancer, and RCC, respectively, from 2004 to 2009. PET scans had been performed for 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with RCC. On regression analysis, a more recent year of diagnosis, younger age, and high stage or grade were predictors of PET scan usage for patients with bladder cancer and RCC. A higher Gleason score and higher D'Amico risk group predicted imaging with prostate cancer.The usage of PET scanning for bladder cancer, prostate cancer, and RCC is increasing but still very selective. The selective use might be driven by a combination of reimbursement constraints and careful identification of the appropriate medical indication.

Mixed acinar-endocrine carcinomas (MAEC) are rare tumors of the pancreas. We present the case of a patient with periampullary tumor that presented with painless jaundice and after investigation was found to have MAEC. He underwent pancreaticoduo-dunectomy with tumor free margins and negative lymph nodes. The patient presented with local recurrence and liver metastasis after 1 year and is on chemotherapy with stable lesions 30 months after the diagnosis.

Background Primary hepatic leiomyosarcoma is a rare disease diagnosed in older aged adults with a median age of 58 and occasionally in children with a history of immunosuppression. Methods From 1998 to 2009, 215 patients were diagnosed with primary hepatic malignancies at our institution, 4 of which were diagnosed with primary hepatic sarcoma (1.8%). Three cases were primary hepatic leiomyosarcomas (LMS) and one case was primary undifferentiated embryonal sarcoma of the liver; median age 30 (range 20-39) years. Results One patient is currently 12 months post-resection with no evidence of recurrence. Two patients passed away at 19 days and 22 months from small for size liver and tumor recurrence respectively. Conclusion We have presented 3 cases of primary hepatic leiomyosarcoma diagnosed at our institution with an unusually young age distribution and no evidence of immunosuppression. These cases highlight the diagnostic and therapeutic challenges of this rare tumour.